633

REVIEWS

HPV Infection in Women: Psychosexual Impact of Genital Warts

and Intraepithelial Lesions

Alessandra Graziottin, MD,* and Audrey Serafini, MD†

*H. San Raffaele Resnati Center of Gynecology and Medical Sexology, Milan, Italy; †IRCCS San Raffaele Department of
Obstetrics and Gynecology, Milan, Italy

DOI: 10.1111/j.1743-6109.2008.01151.x

ABSTRACT

Introduction. Genital Human Papillomavirus (HPV) infection is the most commonly occurring sexually transmitted
viral infection in humans. HPV is a wide family of DNA viruses, which may cause benign skin and mucosal tumors
(genital, anal, or oral warts), intraepithelial neoplasias, and/or malignant cancers in different organs. Women are
more susceptible to the oncogenic effect of HPVs, mostly at the genital site on the uterine cervix.
Aims. This review analyzes the impact of: (i) genital warts (GWs) and their treatment; (ii) HPV-related genital, oral,
and anal precancerous lesions on women’s sexual function.
Methods. A Medline search was carried out. Search terms were HPV, GWs, intraepithelial neoplasia, cervical cancer,
anal cancer, oral cancer, epidemiology, HPV risk factors, sexual dysfunctions, desire disorders, arousal disorders,
dyspareunia, vulvar vestibulitis, vulvodynia, orgasmic difficulties, sexual repertoire, couple sexual problems, depres-
sion, anxiety, pap smear, screening program, therapy, and vaccines.
Main Outcome Measures. Sexual consequences of HPV infection in women, specifically GWs and intraepithelial
HPV-related neoplasia.
Results. Psychosexual vulnerability increases with number of recurrences of HPV infections. Depression, anxiety,
and anger are the emotions most frequently reported. However, to date, there is no conclusive evidence of a specific
correlation between HPV infection and a specific female sexual disorder. The relationship between HPV and vulvar
vestibulitis/vulvodynia-related dyspareunia seems not to be direct. Counseling problems, the role of anti-HPV
vaccine, and the concept of the high-risk partner are discussed. The reader is offered a practical approach with
clinically relevant recommendations that may prove useful in his/her daily practice when dealing with HPV-infected
women and couples.
Conclusion. The evidence of psychosexual consequences of HPV-related GWs and intraepithelial lesions is limited.
Specific research on the sexual impact of GWs and intraepithelial HPV-related lesion in women is urgently needed.
Graziottin A, and Serafini A. HPV infection in women: Psychosexual impact of genital warts and intraepi-
thelial lesions. J Sex Med 2009;6:633–645.
Key Words. HPV; Genital Warts; Intraepithelial Neoplasia; Cervical Cancer; Anal HPV Infection; Oral HPV
Infection; Female Sexual Dysfunctions; Dyspareunia; Psychosexual Issues; HPV Vaccine; High-Risk Partners;
Anxiety; Depression

Introduction or oral warts), or malignant cancers in different

organs. Women are more susceptible to the onco-

G enital Human Papillomavirus (HPV) infec-

tion is the most commonly occurring sexu-
ally transmitted viral infection in humans [1]. HPV
is a wide family of DNA viruses that may cause
benign skin and mucosal tumors (genital, anal,
genic effect of HPVs, mostly at the genital site and
on the uterine cervix [2].
The literature on HPVs is substantial and
increasing. The main areas of research include the
virological characteristics of HPVs, epidemiology,

© 2009 International Society for Sexual Medicine J Sex Med 2009;6:633–645

634
medical and oncological impact of the infection
and related diseases, prevention strategies through
appropriate barrier contraception, pap smear
screening, and the potential role of vaccines [3,4].
However, research investigating the relation-
ship between HPV infections and sexual dysfunc-
tions in women is limited. It is only in recent years
that research in this area has increased. This has
occurred in parallel with the growing rate of infec-
tions and consequent psychosocial burden.
HPV-related diseases may have a significant
impact on women’s sexuality because:
1. It is a sexually transmitted disease (STD)
particularly affecting the vulva and the
uterine cervix. For biological, emotional, and
symbolic reasons, they are the key organs for
women’s eroticism. HPV-related disorders may:
(i) threaten personal and genital health; (ii)
convey the sense of something degrading,
and/or a connotation of stigma, which may
induce the woman to feel ashamed, “dirty”, and
inadequate [5–14]; and (iii) question the health
of the partner and his loyalty and commitment
to the couple, thus potentially affecting sexual
function and raising critical issues for the rela-
tionship [8].
2. It may contribute to vulvodynia and sexual pain
disorders, namely dyspareunia, associated with
and/or consequent to vulvar laser treatment
[15].
3. It is a potentially oncogenic disease, which may
convey a more serious threat for the woman’s
genital and general health, specifically increas-
ing fear and anxiety [5–10,12–14]. Worry asso-
ciated with repeated exams and consultations,
and invasive and painful treatments, which
increase in case of recurrences, adds further
vulnerability to the woman’s emotional and
sexual well-being [8].
The article will analyze the impact of HPVs
infections on women’s psychosexual health.
Medical consequences such as urogenital and
proctological comorbidity will be included when
they interfere with the sexuality of the woman and
the couple.
Method
Given the complexity of the topic, this article will
focus on the impact on women’s sexuality of genital
warts (GWs) and intraepithelial precancerous
lesions. The analysis of HPV psychosexual impact
relies mainly on levels of evidence 2 and 3, along
J Sex Med 2009;6:633–645
Graziottin and Serafini
with the clinical experience of the authors (implied
when no data are referenced). Key articles and
reviews are summarized in primis to give the reader
a full, although concise understanding of the main
characteristics of HPVs, mechanisms of action,
mode of infection, prevention, principles of diag-
nosis, and treatment, and after that, the literature
review was focused on HPV infection’s conse-
quences on women’s psychosexual health. The
search was conducted in Pub Med. Explicit search
terms that enable the search to be replicated were
used. They include: HPV, GWs, intraepithelial
neoplasia, cervical cancer, anal cancer, oral cancer,
epidemiology, HPV risk factors, sexual dysfunc-
tions, desire disorders, arousal disorders, dyspareu-
nia, vulvar vestibulitis, vulvodynia, orgasmic
difficulties, sexual repertoire, couple sexual prob-
lems, medical comorbidities, psychosexual issues,
anxiety, depression, pap-smear, screening program,
therapy, and vaccines. There was no restriction
on geographic setting. The search was limited to
English literature.
A total of 123 studies was collected. Abstracts
and articles were reviewed independently by the
authors. A final list of articles was then deter-
mined. Only 17 articles investigated HPV infec-
tion’s psychosexual consequences as their primary
aim. However, only one was a controlled study [9].
Given the paucity of the controlled studies, all 17
studies were considered, and the level of evidence
was defined as follows: 1a—systematic review of
randomized controlled trials; 1b—individual ran-
domized controlled trial; 2a—systematic review
of cohort study; 2b—individual cohort study;
3a—systematic review of case-control studies;
3b—individual case-control study; 4—case series;
5—expert opinion. Editorials and articles with no
abstract were excluded.
Epidemiology
It is estimated that in the United States alone, 20
million individuals are infected with HPV. Age-
standardized HPV prevalence worldwide has been
shown to vary, nearly 20 times between popula-
tions, from 1.4% in Spain to 25.6% in Nigeria
[16]. Epidemiological studies suggest that about
80% of women will have acquired genital HPV by
age 50, which makes HPV infection the norm
rather than the exception [17–19].
Epidemiology of HPV-related lesions is
further usually differentiated between benign and
precancerous/cancerous lesions:
Psychosexual Impact of HPV Infection in Women
GWs
Dinh et al. collected data on GW diagnosis
history, and on socio-demographic and sexual
behavior variables, from 8,849 sexually active men
and women aged 18 to 59, to determine the per-
centage of subjects who reported having been
diagnosed with GWs in the United States from
1999 to 2004. Overall, 5.6% of 18- to 59-year-old
subjects reported having ever been diagnosed with
GWs. The percentage resulted higher in women
(7.2%) than in men (4%). GW diagnosis peaked
among 25- to 34-year-old women (10.4%) and 35-
to 44-year-old men (6.0%) [20].
Focusing on women, the incidence of GWs
varies in different countries. Robust epidemiologi-
cal data for GWs in Europe comes from the
United Kingdom, where GWs are a notifiable
disease. Epidemiological data for GWs are limited
for other countries in Europe. In France, a recent
prospective observational study estimated an
overall incidence of 228.9 ¥ 100,000 in women
15–65 years [21].
A population-based cross-sectional study in
69,147 women (18–45 years of age) randomly
chosen from the general population in Denmark,
Iceland, Norway, and Sweden reported that 1 in 10
women in the Nordic countries experienced GWs
before the age of 45, with an increasing occurrence
in younger birth cohorts [22]. In southern Europe,
a Spanish study found that 16.9% of women aged
16–20 visiting STD clinics were affected by GW
[23]. In Greece, a cross-sectional study performed
in STD clinics showed that 47% of the sample
of 829 women had GW [24]. A recent Italian
publication estimated the incidence of GWs at
4.3 ¥ 1,000 women in the general female popula-
tion attending gynecological visits [25].
Intraepithelial Neoplasia and Cervical Cancer
HPV types that infect the genital area are classified
as either oncogenic low-risk (e.g., 6, 11, 42, 43, 44)
or oncogenic high-risk types (e.g., 16, 18, 31, 33,
45, 52), according to their associated lesions.
High-risk HPV causes almost all cases of
intraepithelial and invasive cervical cancer (ICC).
This cancer is the second most common cancer
among women worldwide, with an estimated
493,000 new cases and 274,000 deaths in 2002
[26], with 80% of new cases occurring in develop-
ing countries [27,28]. Overall, 70% of ICC cases
were associated with either HPV16 (55%) or 18
(15%). The six next most common types, namely
HPV31, 33, 35, 45, 52, and 58, accounted for an
additional 18% of cases [29]. These cancers take
635
many years to develop, with a peak in risk at about
35–55 years of age [27,28].
Cervical cancer is an important cause of lost
years of life in relatively young women. World-
wide, the ratio of mortality to incidence is 55%,
with higher survival rates and with quite good
prognosis in low-risk regions but with lower sur-
vival in developing countries, where many cases
are present at relatively advanced stages [26].
Main Characteristics and Mechanism of Action
of HPV
Characteristics
HPVs are a group of small DNA viruses. The
double-stranded, circular DNA genomes of all
HPVs are approximately 8 kb in size.
To date, over 100 different viral types have been
identified, and about one-third of these infect epi-
thelial cells in the genital tract. The viral types that
infect the genital tract fall into two categories:
high risk and low risk. The high-risk types are
associated with the development of anogenital
cancers, while infections by the low-risk HPVs
mainly induce benign GWs [30].
The taxonomic status of HPV types, subtypes,
and variants is based on the sequence of their L1
genes, which differ from each other by at least
10%, 2–10%, and 2%, respectively [31]. L1 genes
determine variations in the protein of the viral
capsid, i.e., the container of the DNA virus. Vac-
cines contain the different proteins identifying
genotypes no. 6, 11, 16 and 18, thus inducing
antibodies able to selectively protect against the
viruses specifically identified by the protein-
number-plate [31] (Box 1).
The virus infects keratinocytes in the basal
layers of stratified squamous epithelium of critical
sexual areas such as mouth, vagina, and anus. Cells
in the basal layer consist of stem cells and transit-
amplifying cells that are continuously dividing and
provide a reservoir of cells for the suprabasal
regions. HPV infection of these cells leads to the
activation of a cascade of a viral gene expression
that, perturbing the epithelial cell differentiation,
results, at the end of this cell cycle , in the produc-
tion of HPV virions [32].
In fact, normally, when basal cells undergo cell
division, the daughter cell that migrates into the
suprabasal compartment withdraws from the cell
cycle and initiates a program of terminal differen-
tiation. However, in HPV-positive human kerati-
nocytes and cervical epithelial cells, the suprabasal
J Sex Med 2009;6:633–645
636 Graziottin and Serafini

BOX 1 The New HPV Vaccines: A Hope for the Future

New prophylactic HPV vaccines promise to dramatically reduce the incidence of clinical consequences
of HPV infection, mainly precancerous cervical lesion cervical cancer, and also other precancerous
genital lesions, genital warts, and cytological abnormalities. The quadrivalent vaccine currently
approved by FDA and EMEA utilizes four different “virus-like particles”, thus enabling the immune
system to protect against HPV viruses corresponding to genotypes 6, 11, 16, and 18. This will have a
prophylactic impact on about 90% of condylomata and more than 70% of invasive cervical cancers (the
remaining being caused by others genotypes) [25].
Among children 9–15 years old and young women aged 15–26 years not previously infected with
vaccine-type HPV strains, prophylactic HPV vaccination appears to be highly efficacious [26].
Vaccination is not a substitute for routine cervical screening. Since no vaccine is 100% effective and
not provide protection against non-vaccine HPV types, or against existing HPV infections, routine
cervical screening remains critically important and should follow local recommendations.
The HPV vaccines do not protect against other sexually transmitted diseases, therefore appropriate
precautions against sexually transmitted diseases should continue to be used.

cells continue DNA synthesis and express markers
for cell proliferation [32].
Within this suprabasal compartment, cells
support the amplification of the viral genome, the
expression of capsid genes and the assembly of
progeny virus, and the final encapsidation of HPV
DNA to generate a new virus occurs within the
terminally differentiated cell compartment [32].
Most HPV infections are “cleared” by the
immune system and do not result in clinical dis-
eases [33]. The majority of sexually active adults
will be infected with HPV at least once in their
lives. However, sexually active women less than 25
years of age consistently have the highest rates of
infection [32]. The anatomical characteristics of
the female genital tract, mainly in the genital
mucosal histology, may in part explain female vul-
nerability for clinical sequelae.
Precise mechanisms determining the final
outcomes are currently unknown. When immu-
nocompetence is weakened and/or the virus
belongs to one of the more aggressive oncogenic
subtypes, cancer may finally occur [34]. In
the case of high-risk HPV infection that cause
cervical cancer development, the viral life cycle is
perturbed in two ways: the loss of terminal
differentiation on cell cycle that leads to a cellular
state that cannot support the full viral life
cycle, and the circular viral DNA genome, which
normally resides as a nuclear plasmid, often
becomes integrated into the host genome and
thereby becomes disrupted and its replication
defective.
Types of HPVs, such as HPV-16, HPV-18,
which are designated “high-risk” or “oncogenic,”
have been recognized as causative agents of cervi-
cal, anal, vulvar, and laryngeal cancers. These
sexually transmitted viruses are associated with
more than 70% of cervical cancer cases [34,35].
Clinical Consequences
Clinical sequelae in cases of low-risk HPV infec-
tion consist of GWs, which can cause significant
physical and psychosocial distress.
Respiratory tract papillomatosis are associated
with HPV types 6 and 11; these HPV types are also
commonly associated with GWs. The incidence of
respiratory tract papillomatosis in young adults is
increasing [36–38]. It has been postulated that oro-
genital contact is the means of transmission in this
age group. In view of the high infectivity of GWs,
it is interesting to note the low prevalence of
oro-pharyngeal warts in adults indulging in oro-
genital contact. Clinical manifestations of high-risk
HPV cervical infection include a wide range of
cytological/hystological abnormalities, like abnor-
mal pap test results, low-grade squamous intra-
epithelial lesions (LSIL), high-grade squamous
intraepithelial lesions (HSIL), and cervical cancer.
Other genital sites, such as vulvar and vaginal, could
be the target for high-risk (HR) HPV carcinogen-
esis with comparison of precancerous (high-grade
vulvar intraepithelial neoplasia [VIN] or vaginal
intraepithelial neoplasia [VaIN]) or invasive cancer.
Oral HPV is strongly associated with oral squa-
mous cell carcinoma, suggesting that HPV-16 and
-18 are risk factors for oral cancer [37,38]. A sig-
nificant association with tobacco and alcohol has
been confirmed. In addition, a family history of
cancer is associated with OSCC [36–38].

J Sex Med 2009;6:633–645

Psychosexual Impact of HPV Infection in Women
Anal HPV infections in women are usually
underestimated because women do not think or
report they had unprotected anal sex, and physi-
cians usually do not ask about this sexual practice.
The health risks of unprotected anal sex appear to
be severely underestimated by a substantial pro-
portion of sexually active women and men. Among
heterosexuals, reported rates of condom use are
almost universally lower for anal than for vaginal
intercourse [39]. A U.S. survey and other data
suggest that, in terms of absolute numbers,
approximately seven times more women than
homosexual men engage in unprotected receptive
anal intercourse [39].
Anal intraepithelial neoplasia (AIN) is a con-
sequence of chronic HPV infection in the anal
canal and appears to be driven by high viral loads
of HPV. AIN natural history resembles that
of cervical intraepithelial neoplasia. Low-grade
lesions frequently resolve, but high-grade lesions
are much more stable. HIV-positive men and
women who practice receptive anal intercourse
are at the highest risk of AIN [40]. The incidence
of AIN has increased significantly in the last
decades [41].
Also, the progression of the disease has an
impact on sexual health. The sense of a health
threat can be very different depending on the
grade of the lesions: LSIL vs. HSIL or cancer in
situ, as they require a different aggressiveness of
treatment and follow up.
One of the main biases in the studies surveyed is
that they cluster together lesions of all degrees.
Currently, there are neither effective means of pre-
venting HPV transmission nor cures for clinical
manifestations: infection can only be totally pre-
vented via complete sexual abstinence. Good but
not total protection is achieved when there is con-
sistent condom use during every type of intimacy
(oral, vaginal, anal), and the condom is applied prior
to any contact. Prophylactic VLP L1 vaccines are
now available. They protect women against clinical
consequences of some types of HPV. Bivalent and
quadrivalent formulations protect from HPV
16,18-related cervical cancer and high-grade cervi-
cal intraepithelial neoplasia. Quadrivalent formu-
lations also protect from HPV 6,11,16,18-related
vulvar and vaginal precancerous lesion and GWs.
Treatment for clinical sequelae such as GWs and
precancerous cervical lesion consists of removing
the problematic cells, decreasing HPV viral load,
and watching for recurrence. This method con-
sumes significant health care resources and is costly
[42]. Some costs are difficult to estimate (personal
637
distress, psychological comorbidities, and negative
sexual outcomes).
Diagnosis
The diagnosis of HPV infection and the clinical
consequences can be made following an abnormal
smear test or HPV testing.
Cervical HPV-related lesions are typically
asymptomatic, but in the case of invasive diseases,
some symptoms like atypical vaginal blood losses,
smelly vaginal discharge, urinary or anorectal
symptoms, and weight loss could arise as conse-
quences of malignant proliferation and cancer.
For GWs, visual inspection is normally suffi-
cient for diagnosis.
Therapy
Treatments of precancerous HPV-related lesions
include a wide range of interventions, according to
the type and site of lesions, extension, and severity.
For GWs, both medical and surgical treatments
are available.
Early and late recurrences of the infection and
related pathologies are frequent. They may have a
very different impact from the psychosexual point
of view, according to the severity of lesions,
aggressiveness of related treatments and their side
effects, frequency of recurrences and their severity,
and quality of psychosexual support from relatives
and health care providers.
Psychosexual Impact of HPV Infections
Despite HPV infection being among the most
common STDs seen in clinical practice, attention
has only begun to focus on the psychological or
psychosexual impact of this diagnosis on the indi-
vidual. The few studies that exist suggest adverse
psychological and psychosexual sequelae may be
common [43,44].
Regarding the evaluation of the specific psycho-
sexual impact for different forms of clinical HPV
sequelae, while much research has been published
on the mode of transmission of HPV-related oral
lesions, epidemiology, and other oral disease-
related issues, to the author’s knowledge, no
studies have been published on the psychosexual
consequences of oral HPV infections. The same
consideration could be made of HPV-related anal
lesion; in fact, no specific published literature
exists on psychosexual consequences of anal HPV
infections. So the available studies are focused
J Sex Med 2009;6:633–645
638
on genital—i.e., vulvar/vaginal/cervical—lesions.
However, oral and anal infections are increasing
and should be investigated from the point of view
of their potential psychosexual impact as well.
In the clinical setting, women with flourishing,
massive, disfiguring GWs may express specific
“cosmetic” concerns, at the risk of persistent
modification of the genitals and fears of being
rejected by partners. However, no mention of this
specific issue can be found in the clinical literature
published thus far. Given the increasing focus
women have of the cosmetic appearance of their
genitals and its impact on their self-image and
self-esteem, the cosmetic impact of flourishing
GWs deserves to be specifically evaluated [45].
The evidence emerging from the literature and
from our clinical experience suggests the existence
of several peaks of vulnerability because of HPV
infection. Different stages in the diagnosis and
treatment of HPV infection may have a different
impact on women and couples. The “timing”
effect can overlap with a number of variables,
causing psychosexual impairment or leading to
overt sexual dysfunctions.
Psychosexual Impact of the Diagnosis
HPV testing may offer a number of advantages to
conventional cervical screening, such as increased
sensitivity to high-grade precancerous disease, the
potential to increase screening intervals for HPV
negative women and the reduction of unnecessary
colposcopies among women with borderline
smears. However, HPV testing has been criticized
for its lack of specificity and the potential for large
numbers of women to test positive in the absence
of clinically significant cytological abnormality
[46,47].
Conaglen et al., in their individual case control
study on 101 consecutive clients attending an STD
clinic, evaluated with four validated question-
naires, found that those diagnosed with a first
episode of HPV had considerable psychological
difficulties (25% of the HPV-positive group com-
plained suffering social dysfunction vs. 7.9% of
the HPV-negative group; 17.9% reported severe
depression vs. 10.5%); 29% of men and 10% of
women with a first episode of GWs could be clas-
sified as having sexual concerns at their first visit.
However, the diagnosis of HPV was not associated
with a greater psychological or psychosexual im-
pact than that reported for other sexually trans-
mitted infections [5].
Similar results were reported in a study by
McCaffery et al. [6] A postal questionnaire survey
J Sex Med 2009;6:633–645
Graziottin and Serafini
was sent to 428 women aged 20–64 to measure
psychosocial and psychosexual consequences of
HPV infection. Anxiety, distress, and feelings
about current, past, and future sexual relationships
were also investigated. Women with normal cytol-
ogy who tested positive for HPV were significantly
more anxious and distressed than HPV-negative
women using both a state anxiety measure
F(1,267) = 29, P < 0.0001] and a screening specific
measure of psychological distress F(1,267) = 69,
P < 0.0001]. Women with an abnormal or unsatis-
factory smear result who tested HPV positive were
significantly more distressed than HPV-negative
women with the same smear result F(1,267) = 8.8,
P 1/4 0.002], but there was no significant differ-
ence in the state of anxiety. The HPV-positive
women felt significantly worse about their sexual
relationships. Approximately one-third of women
who tested positive reported feeling worse about
past and future sexual relationships compared with
less than 2% of HPV-negative women.
Even in this investigation, the findings suggest
that testing positive for HPV may have an adverse
psychosocial impact, with increased anxiety, dis-
tress, and concern about sexual relationships [6].
To assess the psychosocial impact of HPV
testing as an adjunct to cytology in routine primary
cervical screening, a controlled study was carried
out. The trial provides a randomized setting of
revealed HPV results vs. concealed results permit-
ting valid comparisons for assessing true psycho-
social impact. The intervention was a revealed
high-risk HPV test result in addition to cervical
cytology. The main outcome was measured using
the General Health Questionnaire (GHQ-28),
Spielberger State–Trait Anxiety Inventory and
Sexual Rating Scale (SRS). Among women with
mildly abnormal or normal cytology, receiving an
HPV (+ve) result did not impact significantly on
GHQ caseness and mean scores or on Spielberger
State and Trait scores when compared with women
in whom the HPV (+ve) test result was concealed.
Among women with normal cytology, receiving an
HPV (+ve) result was associated with a reduction in
the sexual rating scale compared with similar
women whose HPV (+ve) result was concealed. We
can conclude that HPV testing does not add sig-
nificant psychological distress when combined with
cytology in routine primary cervical screening [9].
Maggino et al. [7] evaluated the impact of
the communication of an HPV diagnosis on the
cognitive–behavioral aspect, emotional experi-
ences, psychic–physical well-being, and psycho-
sexual sphere in young women between the ages of
Psychosexual Impact of HPV Infection in Women
20 and 45. Three self-evaluating questionnaires
(the Cognitive Behavioral Assessment-20, the
SAT-P, and the BISF-W) were administered to 36
women who had been diagnosed with an HPV
infection and 36 women who had never been diag-
nosed with HPV. A total of 36% of the experimen-
tal group reacted to the diagnosis with fear, 29%
reacted with anxiety, while only 3% of women did
react with anger. Significant differences emerged
in two samples regarding state of anxiety and
obsessive and compulsive aspects, while there were
no significant differences between the two groups
regarding the subjective satisfaction with life
quality and sexual function. A significant positive
correlation was found between the sum of anxiety
and fear expressed at the time of the diagnosis and
the trait anxiety reported in the CBA-2.0. The
results indicate that the prevalent emotions felt at
the time of the diagnosis are fear and anxiety. The
persons who were diagnosed with an HPV in-
fection resulted as having higher levels of trait
anxiety, obsessions, compulsions, and behaviors
and worries related to hygiene [7].
To evaluate the psychosocial impact of taking
part in repeated testing for HPV, Waller used
in-depth interviews that were carried out with 30
women who were HPV positive with normal
cytology at trial baseline, and attended for a repeat
HPV test 12 months later [8].
This excellent qualitative study indicates that
feelings of shock, confusion, and distress about
testing HPV positive were common. These feel-
ings are frequently related to the sexually trans-
mitted nature of HPV and concerns. They were
articulated about: (i) where the virus had come
from; and (ii) anxiety about the health implications
of HPV. Anxiety was triggered by lack of knowl-
edge about HPV and followed by seeking further
information about HPV from the Internet. Once
some of the confusion had been resolved, women
seemed able to put the result to the back of their
mind until the next test. Particularly reassuring
was the knowledge that the virus could lie dormant
for a long time, so exposure was not necessarily
recent and its presence did not mean that a partner
had been unfaithful [8].
I mean if he’d had an affair with somebody then I would
have been angry and upset. As it is . . . it’s something
that I think he’s had before our relationship, I trust him
a hundred per cent.
Women were also reassured by the fact that
HPV does not cause symptoms, is highly preva-
lent, and can clear spontaneously without treat-
639
ment. The pattern of initial anxiety is modulated
by the attitude of the physician: reassuring vs.
neglecting to clarify the most critical questions
and/or referring the woman to the net.
The only thing that I do go back on is like what is it? If
I keep carrying on, how long will I have it? What will
they do for it? What will the long term effects be for
me? They’re the questions that go over a lot. The other
things are just fleeting thoughts like now I sit and think
about it. Could it be that? Could it be this? Every now
and again I’ll think about it for whatever the reason and
they’re my thoughts that I always have [8].
Not surprisingly, emotional responses following
the second HPV test varied greatly by whether or
not that test was positive. Negative feelings
included fear and anxiety about cancer and becom-
ing ill, concerns about fertility, feelings of being
unclean because of the sexually transmitted nature
of HPV, concerns about transmission and sexual
relationships, a negative impact on feelings about
sex, and relationship issues including blaming a
partner for the infection. Overall, women appeared
to be more distressed by a second HPV-positive
result than a single one, and expressed a clear pre-
ference for immediate colposcopy over continued
surveillance [8].
Psychosexual Impact of the Therapy
HPV genital lesions’ treatment (physical–chemical
therapy, diathermocoagulation, and laser therapy
or pharmacological therapy with imiquimod) is
usually long and painful and can cause sexual
impairments [43,48]. The higher the number of
the interventions, the more painful the technique
and the severity of the scarring, the more severe is
the potential psychosexual impact [43,48]. Unfor-
tunately, while the etiology of the psychosexual
impact has been discussed in different articles, con-
trolled studies on the impact of different therapies
are lacking. Filiberti assessed the psychological and
psychodynamic aspects of patients with widespread
genital HPV infection entering into a clinical trial
in which they were randomly assigned to three
treatment groups: CO2 laser ablation, intramuscu-
lar interferon-alpha, and CO2 laser ablation plus
intramuscolar interferon-alpha. Results indicated
that 57% of the patients experienced sexual impair-
ments after therapy. The main reasons for sexuality
change were: the disease itself, fear of infecting the
partner, pain during the intercourse, and forced
use of condom. Sixteen percent of the patients
reported a worsening of the relationship with the
partner. No difference was found between the dif-
ferent treatment groups [48].
J Sex Med 2009;6:633–645
640
HPV Infection, Vulvodynia, and Dyspareunia
It seems that a link between GWs and vulvodynia
is not due to the clinical HPV-related disease itself
but as consequences of the treatment of the genital
lesions. “Vulvodynia is a prevalent and highly dis-
tressing disorder, with major consequences for
interpersonal and psychological well-being [49].
Vulvodynia is a diverse, multifactorial phenom-
enon that impairs the psychological, physical,
and reproductive health of approximately 10% of
women at some point in their lives [49–53]. The
management of these patients requires a sensitive
provider who can coordinate a multidisciplinary
approach to their care. Despite the lack of large-
scale, placebo-controlled trials, several new treat-
ment options exist [52,54].
Two studies, in fact, do not support the associa-
tion between vulvar HPV infection and vulvodynia
or vulvar vestibulitis. Smith found that a history
of genital infections is associated with an increased
risk of vulvar vestibulitis syndrome (VVS): bacterial
vaginosis (odds ratio, OR = 9.4), Candida albicans
(OR = 5.7), pelvic inflammatory disease (PID)
(OR = 11.2), trichomoniasis (OR = 20.6), and
vulvar dysplasia (OR = l5.7), but no risk associated
with HPV, atypical squamous cells of undeter-
mined significance, cervical dysplasia, GWs,
chlamydia, genital herpes, or gonorrhea [55].
Gaunt et al. investigated the prevalence of HPV
in patients with VVS by using a polymerase chain
reaction (PCR) primer set that detects known
HPV types. They retrospectively identified 38
patients with VVS who underwent therapeutic
surgical excision of the vestibule. Eleven controls
without vestibulitis who underwent vestibular
excision for conditions unrelated to HPV infection
were identified prospectively. Surgical specimens
were examined for the presence of HPV DNA by
PCR amplification. DNA sequencing was used to
determine HPV type. They found that the preva-
lence of HPV among patients with VVS was 21
vs. 36% among controls. Group B HPV types
accounted for 4 of the 10 (40%) HPV types found
in patients with VVS. Overall, in both patient and
control samples, a spectrum of HPV types were
identified, encompassing many branches of the
HPV phylogenetic tree. No etiologic association
was apparent. The low rate of observed infection
in women with and without VVS and the diversity
of HPV types identified suggest incidental virus
carriage rather than direct cause and effect. The
underlying cause of this debilitating condition
remains unknown [56].
J Sex Med 2009;6:633–645
Graziottin and Serafini
Morin [15] found that there was an association
between treatment for vulvar HPV infection and
vulvodynia. This can occur when either pharma-
cologic (Imiquimod) or physical treatment (either
laser or diathermo-coagulation [DTC]) cause per-
sistent introital/vulvar pain as a persistent side
effect of treatment. This negative outcome is
common when physical treatment is:
1. Extensive, because of the magnitude/extension
of the vulvar GWs.
2. Repeated, because of warts’ recurrence or
re-infection.
3. Overzealous (with deep lesions and neuropathic
pain).
4. Associated with a defensive contraction of the
elevator ani, because of the iatrogenic pain.
This, in turn, can contribute to introital dys-
pareunia, reflex inhibition of lubrication, vaginal
dryness and micro-abrasion of the introital
mucosa (during intercourse subsequent to
treatment) and chronic introital inflammation
leading to vulvar vestibulitis and vulvodynia.
The Silent Carrier or the High-Risk Man:
The He-Partner
A specific issue to be dealt with when counseling
women which HPV infections relates to “who
infected whom” [8]. This question becomes more
painful when oncogenic HPV strains are etiologi-
cally related to precancerous lesions that can
progress to cervical or vulvar cancer [7,8]. Studies
assessing the carrier or infected status of partners
of HPV-infected women indicate that subclinical
lesions are far more common than diagnosed by
simple visual genital examination [57,58].
Penile lesions were seen in 68% of the male
sexual partners of women with intraepithelial cer-
vical neoplasia, when examined by visual inspec-
tion, or when available, with the colposcopic
instrument. More than one lesion type was diag-
nosed in 15% of cases. Flat lesions, papular lesions,
and condylomata acuminata were seen in 83%,
29%, and 4% of cases, respectively. HPV was
detected in 59% of the penile scrapings, containing
mainly oncogenic HPV types. When penile lesions
were present, 67% of penile scrapings were positive
for HPV, whereas 37% were HPV-positive when
no lesions were visible. Penile lesions are frequently
found in sexual partners of women with cervical
intraepithelial neoplasia, when appropriately exam-
ined. Most of these lesions are subclinical (i.e., only
visible after acetowhite staining and/or with HPV
Psychosexual Impact of HPV Infection in Women
DNA test of the partner). They are often associated
with the presence of high-risk HPV, indicating that
male sexual partners of women with cervical
intraepithelial neoplasia might constitute a reser-
voir for high-risk HPV [57,58].
Discussion
Women have a gender-specific vulnerability to the
health and sexual consequences of HPV infections.
They have almost twice the percentage of GWs in
comparison with men [20]. Women have a higher
vulnerability to oncogenic HPV, mostly at cervical
and vulvar site. (The age-standardized incidence
of vulvar cancer averages between 1 and 2 per
100,000 women in Western countries. Epidemio-
logical studies have identified sexual factors, par-
ticularly HPV infection, as increasing risk) [59].
The health and sexual risks linked to HPV
infections are currently underestimated by women
themselves.
Research on the specific impact of GWs and
intraepithelial neoplasias on sexual function and
relationship in women is limited. Research focuses
more on general psychological outcomes, such as
depression, anxiety, guilt, anger, rage, or sexuality
as a general issue rather than focusing on specific
dimensions of women’s sexuality [5–14]. To the
author’s knowledge, no studies using validated
sexual questionnaires, such as the Female Sexual
Function Index or Profile of Female Sexual Func-
tion, have been published. The only disorder
investigated to explore if it could be related to
HPV infection is dyspareunia via the link with
vulvodynia/vulvar vestibulitis. However, the rela-
tionship between HPV and vulvar vestibulitis-
related dyspareunia appears to be eventually a
sequelae of the HPV-related diseases treatment
rather than the HPV infection itself [15,55,56].
In previous studies, couple-related psychosexual
issues have only been explored as part of a broader
analysis, with no follow-up studies specifically
examining couple outcomes after treatment for
GWs or intraepithelial neoplasia.
More data have been produced on the impact of
HPV diagnosis on the emotional and psychosexual
well-being.
Communicating the diagnosis, through correct
and exhaustive information on HPV infection and
its psychosexual meaning, should be consistently
offered by the clinician to HPV-positive women
and their partners (if the couple is willing to be
consulted together). Many women are surprised
and upset upon learning about HPV [5–7,10].
641
Many search for information on the Internet and
report being even more scared. Partners may
present with a wide range of negative affects that
should be addressed in parallel [12]. Ensuring that
women are aware that HPV is a common condi-
tion and limiting potential negative consequences
by appropriate follow up and medical interven-
tions (when needed) may reduce the negative feel-
ings and anxiety experienced by women with HPV
[13].
Clinical experience indicates that women with a
satisfying sexuality before the HPV diagnosis are
those less vulnerable to the long-term negative
consequences of GWs and their treatments.
However, controlled studies are needed to support
this claim. Vulnerability increases in women expe-
riencing dysfunctional sexuality prior to diagnosis,
in single women, in women with troubled relation-
ships, or when the infection strongly suggests the
partner has had unprotected sex outside of the
relationship [8]. Clinical correlates include loss of
sexual desire, more difficult mental and genital
arousal, dyspareunia, less frequent intercourse,
and a qualitative and quantitative reduction of the
repertoire of sexual behaviors. After HPV genital
infection, many women refuse further passive oral
sex for fear of infecting their partner.
Overall, preliminary data indicate that sexual
morbidity is more correlated to frequency of
recurrences than to different treatments per se
[48]. Prevention and early diagnosis of recurrences
may reduce the long-term sexual consequences of
HPV infection in women. Active counseling on
potential female sexual dysfunctions worsened or
precipitated by HPV infection should be part of
the routine medical approach.
Physicians should also actively investigate pre-
vious unprotected anal sex in women with genital
HPV infection, to avoid the collusion of silence
and the risk of undiagnosed highly aggressive AIN
[39–41]. After the diagnosis of perianal or anal
HPV-related diseases, many refuse any further
anal intimacy. In the clinical setting, the most fre-
quently reported feeling is a sense of guilt, anal sex
still being considered in many countries as inap-
propriate or even transgressive.
Health care providers should actively inform
women against the risk of unprotected anal sex.
Women are frequently very disturbed to dis-
cover that a partner they loved may have infected
them. “What is the role of men who are sexual
partners of women with genital HPV infection
and/or cancer?” This is a sensitive question
increasingly raised in clinical consultation by
J Sex Med 2009;6:633–645
642
Table 1 HPV infection risk factors and gender vulnerability in women
Youth
Gender (female)
High number of sexual partners
Non-consistently protected sex
Co-infection with chlamydia trachomatis
Co-infection with herpes simplex virus
Smoking
Immunosuppression (HIV, immunosuppressive therapy)
Pregnancy
both affected women and their partners [8]. HPV
testing of the partner, or penis examination,
should be considered part of the diagnostic
assessment of partners of HPV-infected women
[57,58]. The sexual impact of being an inducer or
a carrier or HPV infections should be investi-
gated. Psychosexual and informative counseling
to both partners is critical to prevent further
negative psychosexual outcomes during diagnosis
and treatment of HPV-related lesions. Husbands
and couples express their relief and gratitude
when these issues and potential difficulties and/or
misunderstandings are openly and spontaneously
raised by the physician during the consultation
and when practical suggestions are given to over-
come physical and emotional problems. Guilty
feelings may be pervasive, rooted in the past per-
sonal sex life. On the other hand, aggressive feel-
ings against the partner considered responsible
for the infection (of having “caught” it) and the
subsequent precancerous or cancerous lesions
may dominate the clinical picture in a minority of
cases [7,60–62]. Individual and couple counseling
is critical to addressing these feelings that may
affect the motivational–affective roots of desire
and couple commitment.
Overall, the published data indicate that many
more questions remain unaddressed than answered
in this emerging field of STDs. More research is
needed on all the aspects that remain neglected in
the evaluation of psychosexual outcomes of GWs
and intraepithelial neoplasias. The evidence is
more consistent regarding the outcomes of treat-
ments after cervical, genital, and anal cancers. This
will be reviewed in a separate article.
J Sex Med 2009;6:633–645
Graziottin and Serafini
Moscicki Ab, 2007 [63].
Saleh MM, Seoud AA, Zaklama MS, 2007 [64].
Winer Rl, Feng Q, Hughes JP et al., 2008 [65].
Steben M, Duarte-Franco E, 2007 [66].
Hariri S, Dunne EF, Sternberg M, et al., 1991 [74].
Dinh TH, Sternberg M, Dunne EF, 2008 [20].
Moscicki Ab, 2007 [63].
Saleh MM, Seoud AA, Zaklama MS, 2007 [64].
Winer Rl, Feng Q, Hughes JP et al., 2008 [65].
Epstein RJ, 2005 [67].
Anttila T, Saikku P, Koskela P, et al. 2001 [68].
Bosch FX, de Sanjosè S., 2007 [69].
Ault KA, 2006 [32].
Smith JS, Herrero R, Bosetti C, et al., 2002 [70].
Bosch FX, de Sanjosè S., 2007 [69].
Castellsaguè X, Munoz N. 2003 [71].
Bosch FX, de Sanjosè S., 2007 [69].
Strickler HD, Burk RD, Fazzari M, et al. 2005 [72].
Cameron JE, 2007 [73].
Strickler HD, Burk RD, Fazzari M, et al. 2005 [72].
Conclusions
Women are at an increasing risk of HPV infections
and related lesions, with a specific and underesti-
mated vulnerability to the risk of anal infections
(Table 1). Psychosexual vulnerability increases with
the number of recurrences of HPV infections. Fear,
anxiety, anger, and depression are the emotions
most frequently reported [5–14]. However, to date,
there is no conclusive evidence of a correlation
between HPV infection and a specific female sexual
disorder. The relationship between HPV and
vulvodynia/vulvar vestibulitis-related dyspareunia
seems indirect [15,55,56]. Anti-HPV vaccine may
reduce the incidence of HPV infection and the
related psychosexual consequences [62]. However,
no data have been produced so far on this issue. The
potential of a “high-risk partner” should be consid-
ered and diagnosed while counseling HPV-infected
women. Specific research on the sexual impact of
GWs and intraepithelial HPV-related lesion in
women is urgently needed.
Corresponding Author: Alessandra Graziottin,
MD, Via Enrico Panzacchi 6, 20123 Milano, Italy. Tel:
++39-02-72002177; Fax: ++39-02-876758; E-mail:
a.graziottin@studiograziottin.it.
Conflict of Interest: None declared.
Statement of Authorship
Category 1
(a) Conception and Design
Alessandra Graziottin; Audrey Serafini
(b) Acquisition of Data
Alessandra Graziottin; Audrey Serafini
Psychosexual Impact of HPV Infection in Women
(c) Analysis and Interpretation of Data
Alessandra Graziottin; Audrey Serafini
Category 2
(a) Drafting the Article
Alessandra Graziottin; Audrey Serafini
(b) Revising It for Intellectual Content
Alessandra Graziottin; Audrey Serafini
Category 3
(a) Final Approval of the Completed Article
Alessandra Graziottin; Audrey Serafini
References
1 Capra G, Giovannelli L, Bellavia C, Migliore MC,
Caleca MP, Perino A, Ammatuna P. HPV genotype
prevalence in cytologically abnormal cervical
samples from women living in south Italy. Virus Res
2008;133:195–200.
2 Paavonen J. Human papillomavirus infection and
the development of cervical cancer and related
genital neoplasias. Int J Infect Dis 2007;11
(2 suppl):S3–9.
3 Moscicki AB. Conservative management of adoles-
cents with abnormal cytology and histology. J Natl
Compr Canc Netw 2008;6:101–6.
4 Barr E, Gause CK, Bautista OM, Railkar RA, Lupi-
nacci LC, Insinga RP, Sings HL, Haupt RM.
Impact of a prophylactic quadrivalent human papil-
lomavirus (types 6, 11, 16, 18) L1 virus-like particle
vaccine in a sexually active population of North
American women. Am J Obstet Gynecol 2008;198:
261.e1–11.
5 Conaglen HM, Hughes R, Conaglen JV, Morgan J.
A prospective study of the psychological impact on
patients of first diagnosis of human papillomavirus.
Int J STD AIDS 2001;12:651–8.
6 McCaffery K, Waller J, Forrest S, Cadman L,
Szarewski A, Wardle J. Testing positive for human
papillomavirus in routine cervical screening: Exami-
nation of psychosocial impact. BJOG 2004;111:
1437–43.
7 Maggino T, Casadei D, Panontin E, Fadda E,
Zampieri MC, Donà MA, Soldà M, Altoè G. Impact
of an HPV diagnosis on the quality of life in young
women. Gynecol Oncol 2007;107(1 suppl 1):
S175–9.
8 Waller J, McCaffery K, Kitchner H, Nazroo J,
Wardle J. Women’s experiences of repeated HPV
testing in the context of cervical cancer screening: A
qualitative study. Psychol Oncol 2007;16:196–204.
9 Kitchener HC, Fletcher I, Roberts C, Wheeler P,
Almonte M, Maguire P. The psychosocial impact of
human papillomavirus testing in primary cervical
screening-a study within a randomized trial. Int J
Gynecol Cancer 2008;18:743–8.
643
10 Clarke P, Ebel C, Catotti DN, Stewart S. The psy-
chosocial impact of human papillomavirus infection:
Implications for health care providers. Int J STD
AIDS 1996;7:197–200.
11 Scrivener LD, Green J, Hetherton J, Brook G. Dis-
closure of anogenital warts to sexual partners. Sex
Transm Infect 2008;84:179–82.
12 Harper DM. Why am I scared of HPV? CA Cancer
J Clin 2004;54:245–7.
13 Waller J, Marlow LA, Wardle J. The association
between knowledge of HPV and feelings of stigma,
shame and anxiety. Sex Transm Infect 2007;83:
155–9.
14 Anhang R, Goodman A, Goldie SJ. HPV com-
munication: Review of existing research and recom-
mendations for patient education. CA Cancer J Clin
2004;54:248–59.
15 Morin C, Bouchard C, Brisson J, Fortier M,
Blanchette C, Meisels A. Human papillomaviruses
and vulvar vestibulitis. Obstet Gynecol 2000;95:
683–7.
16 Clifford GM, Gallus S, Herrero R, Muñoz N,
Snijders PJ, Vaccarella S, Anh PT, Ferreccio C,
Hieu NT, Matos E, Molano M, Rajkumar R, Ronco
G, de Sanjosé S, Shin HR, Sukvirach S, Thomas JO,
Tunsakul S, Meijer CJ, Franceschi S, IARC HPV
Surveys Prevalence Study Group. Worldwide distri-
bution of human papillomavirus types in cytologi-
cally normal women in the International Agency for
Research on Cancer HPV prevalence surveys: A
pooled analysis. Lancet 2005;366:991–8.
17 Koutsky LA, Galloway DA, Holmes KK. Epidemi-
ology of genital human papillomavirus infection.
Epidemiol Rev 1988;10:122–63.
18 Myers ER, McCrory DC, Nanda K, Bastian L,
Matchar DB. Mathematical model for the natural
history of human papillomavirus infection and cer-
vical carcinogenesis. Am J Epidemiol 2000;151:
1158–71.
19 Gravitt PE, Jamshidi R. Diagnosis and manage-
ment of oncogenic cervical human papillomavirus
infection. Infect Dis Clin North Am 2005;19:439–
58.
20 Dinh TH, Sternberg M, Dunne EF, Markowitz LE.
Genital warts among 18- to 59-year-olds in the
United States, national health and nutrition exami-
nation survey, 1999–2004. Sex Transm Dis 2008;35:
357–60.
21 Monsonégo J, Breugelmans JG, Bouée S, Lafuma A,
Bénard S, Rémy V. Anogenital warts incidence,
medical management and costs in women consult-
ing gynecologists in France. Gynecol Obstet Fertil
2007;35:107–13.
22 Kjaer SK, Tran TN, Sparen P, Tryggvadottir L,
Munk C, Dasbach E, Liaw KL, Nygård J, Nygård
M. The burden of genital warts: A study of nearly
70,000 women from the general female population
in the 4 Nordic countries. J Infect Dis 2007;196:
1447–54.
J Sex Med 2009;6:633–645
644
23 Orduña Domingo A, Chu JJ, Eiros Bouza JM,
Bratos Pérez MA, Gutiérrez Rodríguez MP,
Almaraz Gómez A, Useros Fernández JL,
Rodríguez Torres A. Age and sex distribution of
sexually transmitted diseases in Valladolid. A study
of 5076 cases. Rev Sanid Hig Publica (Madr)
1991;65:247–58.
24 Kyriakis KP, Hadjivassiliou M, Paparizos VA, Riga
P, Katsambas A. Determinants of GW cases detec-
tion rates among STD clinics in Athens, Greece. Int
J Dermatol 2005;44:650–3.
25 Vittori G, Mateelli A, Boselli F, Naldi L, Emberti
Gialloreti L. Anew approach to estimate Genital
Warts incidence and prevalence in the Italian
general female population. It J Gynaecol Obstet
2008;20:33–42.
26 Parkin DM, Bray F. Chapter 2: The burden of
HPV-related cancers. Vaccine 2006;24S3:S3/11–S3/
25.
27 Schiffman M, Castle PE, Jeronimo J, Rodriguez AC,
Wacholder S. Human papillomavirus and cervical
cancer. Lancet 2007;370:890–907.
28 Parkin DM, Bray F, Ferlay J, Pisani P. Global
cancer statistics, 2002. CA Cancer J Clin
2005;55:74–108.
29 Smith J, Lindsay L, Hoots B, Keys J, Franceschi S,
Winer R, Clifford GM. Human papillomavirus type
distribution in invasive cervical cancer and high-
grade cervical lesions: A meta-analysis update. Int J
Cancer 2007;121:621–32.
30 Longworth MS, Laimins LA. Pathogenesis of
Human Papillomaviruses in Differentiating Epithe-
lia. Microbiol Mol Biol Rev 2004;June:362–72.
31 de Villiers EM, Fauquet C, Broker TR, Bernard
HU, zur Hausen H. Classification of papillomavi-
ruses. Virology 2004;324:17–27.
32 Ault KA. Epidemiology and natural history of
human papillomavirus infections in the female
genital tract. Infect Dis Obstet Gynecol 2006;(2006
suppl):40470.
33 Sellors JW, Karwalajtys TL, Kaczorowski J,
Mahony JB, Lytwyn A, Chong S, Sparrow J, Lorincz
A, Survey of HPV in Ontario Women Group. Inci-
dence, clearance and predictors of human papillo-
mavirus infection in women. CMAJ 2003;168:
421–5.
34 Munger K, Howley PM. Human papillomavirus
immortalization and transformation functions.
Virus Res 2002;89:213–28.
35 Zheng ZM, Baker CC. Papillomavirus genome
structure, expression, and post-transcriptional regu-
lation. Front Biosci 2006;11:2286–302.
36 Clarke J, Terry RM, Lacey CJ. A study to estimate
the prevalence of upper respiratory tract papilloma-
tosis in patients with genital warts. Int J STD AIDS
1991;2:114–5.
37 Campisi G, Panzarella V, Giuliani M, Lajolo C, Di
Fede O, Falaschini S, Di Liberto C, Scully C, Lo
Muzio L. Human papillomavirus: Its identity and
J Sex Med 2009;6:633–645
Graziottin and Serafini
controversial role in oral oncogenesis, premalignant
and malignant lesions (review). Int J Oncol
2007;30:813–23.
38 Anaya-Saavedra G, Ramírez-Amador V, Irigoyen-
Camacho ME, García-Cuellar CM, Guido-Jiménez
M, Méndez-Martínez R, García-Carrancá A. High
association of human papillomavirus infection with
oral cancer: A case-control study. Arch Med Res
2008;39:189–97.
39 Halperin DT. Heterosexual anal intercourse: Preva-
lence, cultural factors, and HIV infection and other
health risks, Part I. AIDS Patient Care STDS
1999;13:717–30.
40 Fox PA. Human papillomavirus and anal intraepi-
thelial neoplasia. Curr Opin Infect Dis 2006;19:
62–6.
41 Parés D, Mullerat J, Pera M. Anal intraepithelial
neoplasia. Med Clin (Barc) 2006;127:749–55.
42 Fleurence RL, Dixon JM, Milanova TF, Beusterien
KM. Review of the economic and quality of life
burden of cervical Human papillomavirus disease.
AJOG 2007;196:206–12.
43 Linnehan MJ, Groce NE. Counseling and educa-
tional interventions for women with genital human
papillomavirus infection. AIDS Patient Care STDS
2000;14:439–45.
44 Voog E, Löwhagen GB. Follow-up of men with
genital papillomavirus infection: Psychosexual
aspects. Acta Derm Venereol 1992;72:185–6.
45 Goodman MP, Bachmann G, Johnson C, Fourcroy
JL, Goldstein A, Goldstein G, Sklar S. Is elective
vulvar plastic surgery ever warranted, and what
screening should be conducted preoperatively? J Sex
Med 2007;4:269–76.
46 Woodman CB, Collins S, Winter H, Bailey A, Ellis
J, Prior P, Yates M, Rollason TP, Young LS. The
natural history of cervical human papillomavirus
infection in young women: A longitudinal cohort
study. Lancet 2001;357:1831–6.
47 Miller AB. Natural history of cervical human papil-
lomavirus infections. Lancet 2001;357:1816.
48 Filiberti A, Tamburini M, Stefanon B, Merola M,
Bandieramonte G, Ventafridda V, De Palo G. Psy-
chological aspects of genital human papillomavirus
infection: A preliminary report. J Psychosom Obstet
Gynaecol 1993;14:145–52.
49 Bachmann G, Rosen R, Pinn V, Utian W, Ayers C,
Basson R, Binik Y, Brown C, Foster D, Gibbons J,
Goldstein I, Graziottin A, Haefner H, Harlow B,
Kellogg Spadt S, Leiblum S, Masheb R, Reed B,
Sobel J, Veasley C, Wesselmann U, Witkin S. Vul-
vodynia: A state-of-the-art consensus on definitions,
diagnosis and management. J Reprod Med 2006;51:
447–56.
50 Graziottin A, Brotto LA. Vulvar vestibulitis syn-
drome: A clinical approach. J Sex Marital Ther
2004;30:125–39.
51 Zolnoun D, Hartmann K, Lamvu G, As-Sanie S,
Maixner W, Steege J. A conceptual model for the
Psychosexual Impact of HPV Infection in Women
pathophysiology of vulvar vestibulitis syndrome.
Obstet Gynecol Surv 2006;61:395–401.
52 Goldstein AT, Burrows L. Vulvodynia. J Sex Med
2008;5:5–14.
53 Greenstein A, Ben-Aroya Z, Fass O, Militscher I,
Roslik Y, Chen J, Abramov L. Vulvar vestibulitis
syndrome and estrogen dose of oral contraceptive
pills. J Sex Med 2007;4:1679–83.
54 Pukall C, Kandyba K, Amsel R, Khalifé S, Binik Y.
Effectiveness of hypnosis for the treatment of vulvar
vestibulitis syndrome: A preliminary investigation.
J Sex Med 2007;4:417–25.
55 Smith EM, Ritchie JM, Galask R, Pugh EE, Jia J,
Ricks-McGillan J. Case-control study of vulvar ves-
tibulitis risk associated with genital infections. Infect
Dis Obstet Gynecol 2002;10:193–202.
56 Gaunt G, Good AE, McGovern RM, Stanhope
CR, Gostout BS. Human papillomavirus in vulvar
vestibulitis syndrome. J Reprod Med 2007;52:485–
9.
57 Bleeker MC, Hogewoning CJ, Van Den Brule AJ,
Voorhorst FJ, Van Andel RE, Risse EK, Starink
TM, Meijer CJ. Penile lesions and human papillo-
mavirus in male sexual partners of women with cer-
vical intraepithelial neoplasia. J Am Acad Dermatol
2002;47:351–7.
58 Bleeker MC, Snijders PF, Voorhorst FJ, Meijer CJ.
Flat penile lesions: The infectious “invisible” link in
the transmission of human papillomavirus. Int J
Cancer 2006;119:2505–12.62.
59 Giles GG, Kneale BL. Vulvar cancer: The Cinder-
ella of gynaecological oncology. Aust N Z J Obstet
Gynaecol 1995;35:71–5.
60 Grassi L, Indelli M, Marzola M, Maestri A, Santini
A, Piva E, Boccalon M. Depressive symptoms and
quality of life in home care assisted cancer patients.
J Pain & Sympt Mgmt 1996;12:300–7.
61 Seibel M, Freeman M, Graves WL. Carcinoma of
the cervix and sexual function. Obstet Gynecol
1980;55:484–7.
62 Rambout L, Hopkins L, Hutton B, Fergusson D.
Prophylactic vaccination against human papilloma-
virus infection and disease in women: A systematic
review of randomized controlled trials. CMAJ
2007;177:469–79.
63 Moscicki AB. HPV infections in adolescents. Dis
Markers 2007;23:229–34.
64 Saleh MM, Seoud AA, Zaklama MS. Study of
the demographic criteria and management of
645
adolescents referred with abnormal cervical smears.
J Obstet Gynaecol 2007;27:824–7.
65 Winer RL, Feng Q, Hughes JP, O’Reilly S, Kiviat
NB, Koutsky LA. Risk of female human papilloma-
virus acquisition associated with first male sex
partner. J Infect Dis 2008;197:279–82.
66 Steben M, Duarte-Franco E. Human papillomavi-
rus infection: Epidemiology and pathophysiology.
Gynecol Oncol 2007;2(107 suppl):S2–5.
67 Epstein RJ. Primary prevention of human
papillomavirus-dependent neoplasia: No condom,
no sex. Eur J Cancer 2005;41:2595–600.
68 Anttila T, Saikku P, Koskela P, Bloigu A, Dillner J,
Ikäheimo I, Jellum E, Lehtinen M, Lenner P,
Hakulinen T, Närvänen A, Pukkala E, Thoresen S,
Youngman L, Paavonen J. Serotypes of Chlamydia
trachomatis and risk for development of cervical
squamous cell carcinoma. JAMA 2001;285:47–51.
69 Bosch FX, de Sanjosé S. The epidemiology of
human papillomavirus infection and cervical cancer.
Dis Markers 2007;23:213–27.
70 Smith JS, Herrero R, Bosetti C, Muñoz N, Bosch
FX, Eluf-Neto J, Castellsagué X, Meijer CJ, Van
den Brule AJ, Franceschi S, Ashley R, International
Agency for Research on Cancer (IARC) Multicen-
tric Cervical Cancer Study Group. Herpes simplex
virus-2 as a human papillomavirus cofactor in the
etiology of invasive cervical cancer. J Natl Cancer
Inst 2002;94:1604–13.
71 Castellsaguè X, Munoz N. Chapter 3: Cofactors
in human papillomavirus carcinogenesis: Role of
parity, oral contraceptives, and tobacco smoking.
J Natl Cancer Inst Monogr 2003;31:20–8.
72 Strickler HD, Burk RD, Fazzari M, Anastos K,
Minkoff H, Massad LS, Hall C, Bacon M, Levine
AM, Watts DH, Silverberg MJ, Xue X, Schlecht
NF, Melnick S, Palefsky JM. Natural history and
possible reactivation of human papillomavirus in
human immunodeficiency virus-positive women.
J Natl Cancer Inst 2005;97:577–86.
73 Cameron JE, Hagensee ME. Human papillomavirus
infection and disease in the HIV+ individual. Cancer
Treat Res 2007;133:185–213.
74 Hariri S, Dunne EF, Sternberg M, Unger ER,
Meadows KS, Karem KL, Markowitz LE. Seroepi-
demiology of human papillomavirus type 11 in the
United States: Results from the third national health
and nutrition examination survey, 1991–1994. Sex
Transm Dis 2008;35:298–303.
J Sex Med 2009;6:633–645